ThepqrABOperon Is Responsible for Paraquat Resistance inStreptomyces coelicolor

Abstract

Paraquat (methyl viologen)-resistant mutants of Streptomyces coelicolor A3(2) that grew and sporulated normally in the presence of paraquat were isolated. Based on the positions of the mutant loci in the genetic map, we isolated the pqr (paraquat resistance) gene whose mutation (pqr501) caused a dominant paraquatresistant phenotype. The pqr locus consists of two genes (pqrA and pqrB) that form a transcription unit. The pqrA gene encodes a protein with a TetR-like DNA-binding motif, and the pqrB gene encodes a putative efflux pump of the major facilitator superfamily. The pqr501 mutation was a base substitution changing arginine-18 to glutamine (R18Q) near the helix-turn-helix motif in PqrA. A pqrA null mutant exhibited similar paraquat resistance, and an increase in the amount of pqrA promoter-driven transcripts of about eightfold was observed for the pqrA501 mutant. These results suggest that PqrA is a negative regulator of its own operon. Deletion of the pqrAB operon caused cells to be very sensitive to paraquat, consistent with the prediction that PqrB may function as a paraquat-efflux pump. Purified PqrA protein specifically bound to the pqrA promoter region, whereas mutant R18Q protein did not, indicating that PqrA is a direct autoregulator of its own operon.

Bacillus subtilisLmrA Is a Repressor of thelmrABandyxaGHOperons: Identification of Its Binding Site and Functional Analysis oflmrBandyxaGH

“…(11,13). A similar situation has been reported for the Streptomyces coelicolor A3(2) pqrAB operon regarding paraquat resistance (6). PqrA is a TetR family repressor of its own operon, and PqrB is a putative efflux transporter of paraquat.…”

Bacillus subtilis Paraquat Resistance Is Directed by σ M , an Extracytoplasmic Function Sigma Factor, and Is Conferred by YqjL and BcrC

“…SmvA is similar to the MvrA protein of E. coli (17,29). A similar efflux system has been identified in S. coelicolor encoded by the pqrAB operon (9). The PqrA protein is a predicted transcriptional repressor, while PqrB is an MvrA/SmvA ortholog.…”

“…The PqrA protein is a predicted transcriptional repressor, while PqrB is an MvrA/SmvA ortholog. B. subtilis contains a similarly organized operon (yvkBA) that may also play a role in PQ resistance (9); however, the yvkBA operon was not identified in global surveys of B. subtilis genes inducible by PQ or other oxidative stress agents (15,23,30), nor has expression of yvkBA been linked to M (1,44). To identify genes that may play a role in PQ resistance, we analyzed null mutants defective for each of nine different Mdependent genes.…”

A multidrug efflux system is involved in colony growth in Streptomyces lividans

“…In Streptomyces, divergently oriented regulator-pump pairs have also been found in antibiotic biosynthesis gene clusters, such as tcmR/tcmA in the tetracenomycin cluster (Guilfoile & Hutchinson, 1992), actII-orf1/actII-orf2 in the actinorhodin cluster (Fernandez-Moreno et al, 1991), rifP/rifQ in the rifamycin cluster (August et al, 1998) and lanJ/lanK in the landomycin cluster (Westrich et al, 1999). In the pqrAB operon of S. coelicolor, mutations in a TetR-type regulatory gene, pqrA, result in derepression of the efflux gene, pqrB, and elevated resistance to paraquat (Cho et al, 2003). PqrA is also its own repressor.…”

“…PqrB) in S. coelicolor (Cho et al, 2003) and S. avermitilis, and among known resistance pumps in other actinomycetes, such as SgcB of Streptomyces globisporus (Liu & Shen, 2000), LfrA of Mycobacterium smegmatis (Takiff et al, 1996), RifP of Amycolatopsis mediterranei (August et al, 1998) and VarS of Streptomyces virginiae (Lee et al, 1999).…”